Parasitism refers to a close relationship between two dissimilar organisms in which one organism (the parasite) benefits at the expense of the host. Parasitology often refers to protozoa and helminthic infections, but all pathogenic microbes face the same pressures to evade immune killing and derive nutrients in order survive in their mammalian hosts. This application is based on the hypothesis that the mechanisms through which pathogenic microbes invade and elicit disease in mammalian hosts, and responses of the host to these microbial pathogens, will share common features among microbes from different phyla, i.e., protozoa, helminths, bacteria, and viruses. A corollary is that the same technology can be applied to investigations of microbial virulence/host responses to different pathogens. Advances in microbial and host proteomics, metabolomics, deep-sequencing, regulatory RNAs and imaging have dramatically changed our capacity to approach critical questions underlying the host-parasite relationship. This Mechanisms of Parasitism training program embodies an integrated approach to the study of parasitism among researchers studying different pathogenic microbes but sharing interests in the survival mechanisms of the microbe and the defense strategies of the host. During the 14 years since its initial funding, the Mechanisms of Parasitism program has supported a total of 63 trainees (34 predocs and 29 postdocs). Virtually all of these trainees remain in science today, many early ones of whom are now in tenured academic positions. Key features of our program have been a weekly Parasitism Journal Club/Research meeting, annual formal presentations of the entire program, sponsored outside speakers, and mechanisms to promote the use of new technology and equipment by our trainees. Our ratios of applicants to selected trainees are high (13:1 predoc and 11:1 postdoc) and we expect postdoc applications to increase even further. In this application we request to (1) increase from 3 to 4 postdoctoral positions; (2) continue supporting 4 predoctoral trainees per year; (3) expand our weekly research meetings to include Technical Topics intended to provide trainees with the background and functional use of the latest techniques in bioinformatics, proteomics, statistics and statistical genetics, and microscopy; (4) expand our involvement of trainees in inviting and hosting outside speakers, and (5) focus on career development needs unique to the current research climate. Our program has been highly productive over the past 14 years. Our goal is to creatively and continually improve the environment and opportunities for trainees working on different aspects of the host-microbe balance during microbial infection.